Neurokinin-1 receptor mediated breast cancer cell migration by increased expression of MMP-2 and MMP-14

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• 作者：Jingyi Li ; Qian Zeng ; Yixin Zhang ; Xiaofang Li ; Hui Hu ; Xiaokang Miao ; Wenle Yang ; Wei Zhang ; Xiaoyun Song ; Lingyun Mou ; ^{muly@lzu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Rui Wang ; ^{wangrui@lzu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AP-1 ; activator protein-1 ; NF-κB ; nuclear factor kappa B ; ERK1/2 ; extracellular regulated protein kinases1/2 ; JNK ; c-jun N-terminal kinase
• 刊名：European Journal of Cell Biology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：95
• 期：10
• 页码：368-377
• 全文大小：2257 K

文摘

Breast cancer (BC) is a common reason of cancer-associated death in female. To develop novel strategy of therapeutics, it is crucial to comprehensively understand the receptor status of BC cells on the surface and inner, because chemical messengers can bind the receptors and promote tumorigenesis. Compared with normal and benign samples, BC cell lines and malignant biopsies showed higher expression of neurokinin-1 receptor (NK1). In current work, we examined the role and mechanism of NK1 receptor signaling in BC cell migration. Human hemokinin-1 (hHK-1) was the peripheral agonist of NK1 receptor. Our results showed that by activating NK1 receptor, hHK-1 promoted the migration of BC cells. Gelatin zymography and WB experiment showed that hHK-1 enhanced the levels of MMP-2 and MMP-14; inhibition of these two MMPs blocked hHK-1-induced cell migration. We further explored the underlying mechanism. hHK-1 incuced the phosphorylation of ERK1/2, JNK and Akt through PKC or PKA pathway. The phosphorylation of these kinases further regulated the activation of transcriptional factor AP-1 and NF-κB. Inhibition of AP-1 and NF-κB reduced the up-regulation of MMP-2 and MMP-14 by hHK-1. Taken together, we showed NK1 receptor was an important regulator of human BC cell migration and a potential target for BC treatment.